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Journal of Immunology Research
Volume 2015, Article ID 348798, 16 pages
http://dx.doi.org/10.1155/2015/348798
Review Article

The Novel PKCθ from Benchtop to Clinic

1Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, and Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut, Lebanon
2Department of Biomedical Science, Faculty of Health Sciences, Global University, P.O. Box 15-5085, Batrakiyye, Beirut, Lebanon
3Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Riad El Solh, Beirut, Lebanon

Received 1 August 2014; Accepted 12 January 2015

Academic Editor: Douglas C. Hooper

Copyright © 2015 Rouba Hage-Sleiman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The protein kinases C (PKCs) are a family of serine/threonine kinases involved in regulating multiple essential cellular processes such as survival, proliferation, and differentiation. Of particular interest is the novel, calcium-independent PKCθ which plays a central role in immune responses. PKCθ shares structural similarities with other PKC family members, mainly consisting of an N-terminal regulatory domain and a C-terminal catalytic domain tethered by a hinge region. This isozyme, however, is unique in that it translocates to the immunological synapse between a T cell and an antigen-presenting cell (APC) upon T cell receptor-peptide MHC recognition. Thereafter, PKCθ interacts physically and functionally with downstream effectors to mediate T cell activation and differentiation, subsequently leading to inflammation. PKCθ-specific perturbations have been identified in several diseases, most notably autoimmune disorders, and hence the modulation of its activity presents an attractive therapeutic intervention. To that end, many inhibitors of PKCs and PKCθ have been developed and tested in preclinical and clinical studies. And although selectivity remains a challenge, results are promising for the future development of effective PKCθ inhibitors that would greatly advance the treatment of several T-cell mediated diseases.